Budget Amount *help |
¥199,940,000 (Direct Cost: ¥153,800,000、Indirect Cost: ¥46,140,000)
Fiscal Year 2019: ¥39,780,000 (Direct Cost: ¥30,600,000、Indirect Cost: ¥9,180,000)
Fiscal Year 2018: ¥39,130,000 (Direct Cost: ¥30,100,000、Indirect Cost: ¥9,030,000)
Fiscal Year 2017: ¥39,390,000 (Direct Cost: ¥30,300,000、Indirect Cost: ¥9,090,000)
Fiscal Year 2016: ¥41,210,000 (Direct Cost: ¥31,700,000、Indirect Cost: ¥9,510,000)
Fiscal Year 2015: ¥40,430,000 (Direct Cost: ¥31,100,000、Indirect Cost: ¥9,330,000)
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Outline of Final Research Achievements |
We established skeletal muscle-specific Akt1/2 double knockout (mAktDKO) mice, as a mouse model mimicking premature sarcopenia in humans, and revealed that they exhibited accelerated muscle volume reduction, locomotive dysfunction, insulin resistance, and systemic senescence. In skeletal muscle of the mAktDKO mice, decreased mitochondria and mitophagy failure were observed, and the former was attributed to the mTOR pathway, a key pathway downstream of Akt, whereas the latter was to the FoxO pathway, the other key pathway. Inhibition of FoxO activity was sufficient in the maintenance of muscle volume. The mAktDKO mice showed osteoporosis and shortened lifespan mainly due to debilitation, which mimicked aging and frailty in humans. We also generated a model of sarcopenic obesity by feeding the mAktDKO mice with high-fat diet, which exhibited shortened lifespan mainly due to tumor death, suggesting that skeletal muscle could be involved in the regulation of systemic tumor resistance.
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